Dual role of IL-7 in the growth and differentiation of immature thymocytes.

The effects of interleukin 7 (IL-7) on subpopulations of CD4-CD8- thymocytes from young adult mice were tested in vitro. When highly purified CD3-CD4-CD8-thymocytes were cultured in the presence of recombinant IL-7, significant proportions of them became CD4+ and/or CD8+ within a day. CD3+ cells were also detected after 2 days. CD3-CD4-CD8- thymocytes were further subdivided into interleukin 2 receptor (IL-2R)- and IL-2R+ populations. The majority of the IL-2R- cells became CD4+ and/or CD8+ in 1 day in the presence of IL-7, and a substantial proportion of them also became CD3+ in 2-3 days. No significant number of CD4+ or CD8+ cells were generated from the IL-2R+ population under the same conditions. However, a small but significant proportion of them became CD3+ in 3-day cultures with IL-7. Although CD4+/CD8+ cells were also generated from the IL-2R- population in 1-day cultures in the absence of IL-7, the viability of the cells declined rapidly, and no significant numbers of CD3+ cells were generated. In proliferation assays, IL-7 alone vigorously stimulated relatively minor subpopulations of CD4-CD8- thymocytes. The IL-7-responsive cells were CD3+, did not express the IL-2R or the heat-stable antigen M1/69, and included both T-cell receptor (TCR)alpha beta + and TCR alpha beta- populations, the latter most likely TCR gamma delta +. The CD3+CD4-CD8- thymocytes, stimulated with IL-7 for 3 days, remained CD4-CD8-. These results demonstrate important roles of IL-7 in the growth and differentiation of CD4-CD8- thymocytes in vitro. It functions as a survival factor and allows CD3-CD4-CD8- cells to undergo their precommitted differentiation without inducing their proliferation, and it also stimulates CD3+CD4-CD8-thymocytes to proliferate without inducing their differentiation.